PROJECT SUMMARY Men are found to contribute to infertility in >40% of the cases and are solely the cause in 30% of the cases. Semen analysis is considered critical and in many instances is the first recourse in male infertility evaluation. Seminal quality is evaluated by determining the sperm concentration, motility, and morphology. Manual microscope-based testing and computer-assisted semen analysis (CASA) systems are the current standard methods to measure semen quality; however, they are labor-intensive, expensive, and laboratory-based. A majority of fertility clinics and small hospitals cannot afford the expensive CASA platforms available in the market and so use a less accurate and subjective manual method for semen analysis. CASA technique requires highly trained technicians for producing reliable and repeatable results. Also, manual test results are subjective making it difficult to compare results from different clinics. Infertility in resource-limited settings is also a global issue and being able to provide routine, point-of-care testing is needed. Global health experts have made infertility a major issue and have expressed interest in low-cost and simple point-of-care testing. Further, the majority of men don't go for follow up semen analysis tests after vasectomy procedure. Male experience in giving a semen sample at fertility clinics is poor. Men have to provide semen samples in the special rooms at a hospital, a situation in which they often experience stress, embarrassment, pessimism, and disappointment. A point-of-care diagnostic assay for home-based male infertility detection through sperm count and motility measurement is of paramount importance and can shift the paradigm in infertility diagnosis and management in both developed and developing countries. To the best of our knowledge, there is currently no point-of-care assay in the market or development pipeline that can efficiently, reliably, and rapidly measure (i) sperm linear and curvilinear velocities, (ii) sperm motility and progressive motility, and (iii) sperm concentration in a real-time fashion. Here, we propose to develop the first automated, rapid, sensitive, and inexpensive smartphone-based diagnostic assay with the potential to make men fertility testing as accessible, easy, fast, and private as pregnancy tests for women. To address all of the technical challenges in developing a true point-of-care, home-based semen analysis tool, we have invented a microchip technology (International utility patent# PHC 025685) that uniquely integrates (i) hardware optics using a unique combination of two aspheric lenses for image magnification, (ii) a novel microfluidic design for easy-to-use semen sample handling based on WHO guidelines for semen analysis done by a non-expert user, and (iii) a novel image processing algorithm that enables rapid (~5 seconds), on-phone image processing utilizing videos recorded from undiluted, unwashed human semen samples.